1. Field of the Invention
The present invention relates to cosmetic cosmetic or dermatological preparations having a content of one or more thiazoles against unwanted pigmentation of the skin.
2. Discussion of Background Information
Melanocytes are responsible for pigmentation of the skin and may be found in the lowest layer of the epidermis, the Stratum basale, in addition to the basal cells as pigment-forming cells—occurring according to skin type either singly or more or less aggregated.
Melanocytes contain as characteristic cell organelle melanosomes, in which the melanin is formed. Melanin is formed to an increased extent, inter alia, on excitation by UV radiation. The melanin is transported via the living layers of the epidermis (keratinocytes) ultimately into the Horny layer (corneocytes) and gives rise to a more of less expressed brownish to brown-black skin color.
Melanin is formed as the last step of an oxidative process in which tyrosine, with the participation of the enzyme tyrosinase, is converted via a plurality of intermediates to the brown to brown-black eumelanins (DHICA and DHI melanin), or with the participation of sulfur compounds to form the reddish pheomelanin. DHICA and DHI melanin are formed via the shared intermediates dopaquinone and dopachrome. The latter is converted, in part with the participation of further enzymes either into indole-5,6-quinonecarboxylic acid or indole-5,6-quinone, from which the two aforementioned eumelanins are formed.
The formation of pheomelanin proceeds, inter alia, via the intermediates dopaquinone and cysteinyldopa. The expression of the melanin-synthesizing enzymes is controlled by a specific transcription factor (microphthalmia-associated transcription factor, MITF). In addition to the described enzymatic processes of melanin synthesis, in the melanosomes, still further proteins are important for melanogenesis. An important role appears to be assigned here to what is termed p-protein, the exact function is still unclear.
Apart from the above described process of melanin synthesis in the melanocytes, in the pigmentation of the skin, the transfer of the melanosomes, the remaining thereof in the epidermis and also the breakdown thereof and breakdown of the melanin are also of critical importance. It has been found that for the transport of melanosomes from the melanocytes into the keratinocytes, the PAR-2 receptor is of importance (M. Seiberg et al., 2000, J. Cell. Sci., 113: 3093-101).
In addition, size and shape of the melanosomes have an effect on their light-scattering properties and therefore the skin color appearance. Thus, in black Africans, large spheroidal melanosomes singly are found to a greater extent, whereas in Caucasians, somewhat smaller melanosomes occurring in groups are found.
Problems with hyperpigmentation of the skin have varied causes, or are associated symptoms of many biological processes, e.g. UV radiation (e.g. freckles, Ephelides), genetic disposition, disturbed pigmentation of the skin on wound healing or scar formation (post-inflammatory hyperpigmentation) or on skin ageing (e.g. Lentigines seniles).
After inflammatory reactions, the pigmentation system of the skin reacts with sometimes opposing reactions. Both post-inflammatory hyperpigmentations and also hypopigmentations can occur. Post-inflammatory hypomelanoses frequently occur, inter alia, in combination with atopy, Lupus erythematosus and psoriasis. The under-standing of the varying forms of reaction of the pigmentation system of human skin as a consequence of inflammatory symptoms is very incomplete.
Problems with post-inflammatory hyperpigmentation frequently occur with darker skin types. Especially in dark-skinned males, the problem of Pseudofollikulitis barbae is known, which is accompanied with cosmetically undesirable pigmentation disorders or is followed thereby. Also forms of melasma which occur especially in the face and décolleté regions of women of Asiatic origin, and also various types of irregular pigmentation of the skin are included in the post-inflammatory hyperpigmentations. In addition, dark eye rings are also considered to be a type of post-inflammatory hyperpigmentation, wherein the underlying inflammation usually proceeds subclinically.
In many cases, such post-inflammatory pigmentation disorders are further increased by the action of sunlight (UV light), without a UV-induced inflammation (sunburn) occurring.
Active ingredients and preparations are known which counteract skin pigmentation. Those in practical use are substantially formulations based on hydroquinone, some of which, however, only display their activity after application for several weeks, the excessively long application of which, on the other hand, is of concern for toxicological reasons. Albert Kligman et al. developed what is termed a “triformula” which is a combination of 0.1% Tretinoin, 5.0% hydroquinone, 0.1% dexamethasone (A. Kligman, 1975, Arch. Dermatol., 111: 40-48). However, this formulation is also highly controversial because of possible irreversible changes in the pigmentation system of the skin.
In addition, skin-peeling methods (chemical and mechanical peelings) are used, but which frequently are followed by inflammatory reactions, and owing to post-inflammatory hyperpigmentations occurring thereafter can even lead to greater rather than reduced pigmentation. All of these familiar methods which are also used for treating post-inflammatory hyperpigmentations, are distinguished by substantial side effects.
Therefore, it was the aim of the following invention to provide a remedy for the disadvantageous prior art.